The present invention relates generally to immunization and immunotherapy for the treatment or prevention of HIV. In particular, the methods relate to in vivo and ex vivo enrichment of HIV-specific CD4 T cells. In certain embodiments, the disclosed compositions and methods can incorporate therapy in order to further enhance the HIV-specific CD4 T cells.

Compounds that either produced a higher proportion or greater absolute number of phenotypically identified naive, stem cell memory, central memory T cells, adaptive NK cells, and type I NKT cells are identified. Compositions and methods for modulating immune cells including T, NK, and NKT cells for adoptive cell therapies with improved efficacy are provided.

The invention provides a modified T cell, or an isolated population of immune cells expressing a CXCR3 isoform selected from CXCR3A, CXCR3B, and CXCR3alt, and optionally, further expressing transgenes comprising an artificial T cell receptor, and/or a CXCR3 ligand, for use as a medicament. The invention also provides the methods to obtain said cells, or populations of cells from a plurality of immune cells derived from a human subject. The invention also relates to assessment of CXCR3 splice variants and its ligands CXCL9, CXCL10, and CXCL11 in muscle-invasive bladder cancer (MIBC) patients, to enable patients to be stratified for their predicted response to a chemotherapy drug treatment, or clinical outcome.

Provided are engineered cells (such as stem cells or T cells) that have a surface molecule comprising a membrane-tethered binding moiety that binds to a T cell surface antigen (such as CCR5, CD4 or CXCR4) or a HIV antigen, or a membrane tethered inhibitory moiety that inhibits the membrane fusion of HIV (such as C34). Also provided are methods of making and using these engineered cells.

This invention provides, as a therapeutic method for eradication of neoplastic diseases of the blood with poor diagnosis, a cell co-expressing a chimeric antigen receptor (CAR) protein and a CXCL12 receptor protein on the cell membrane, and an agent and a pharmaceutical composition having anti-tumor activity, which comprises such cell.

The present disclosure provides anti-CCR4 chimeric antigen receptors (CARs) and compositions and methods for modified immune cells or precursors thereof (e.g., modified T cells) comprising anti-CCR4 CARs. Also provided are methods of using the anti-CCR4 CAR-expressing cells to treat cancer and T cell-depleting systems for use in combination with anti-CCR4 CAR T cell therapy.

This invention is directed to the treatment of cancers, e.g., inflammatory breast cancer, with NK (natural killer) cells wherein the cells are modified ex vivo such that their ability to overcome the chemorepellant effect of a tumor is enhanced. The cells may be genetically modified ex vivo and/or modified by contacting the cells ex vivo with an anti-chemorepellant agent. This invention also provides ex vivo modified NK cells, which are modified such that they express no or substantially no CXCR4 on their cell surface, or express CXCR7, or express a chimeric antigen receptor, or combinations thereof. The invention also relates to methods for treating a patient having a tumor, e.g., inflammatory breast cancer, by administering the modified NK cells, with or without treatment with other conventional anticancer treatments, e.g. , chemotherapy, radiotherapy, viral therapies, hormonal therapies, as well as other immunotherapies and anti-chemorepellant therapies.

The present invention relates generally to immunization and immunotherapy for the treatment or prevention of HIV. In particular, the methods relate to in vivo and ex vivo enrichment of HIV-specific CD4 T cells. In certain embodiments, the disclosed compositions and methods can incorporate therapy in order to further enhance the HIV-specific CD4 T cells.

A therapeutic combination for treating cancer in a subject having a tumor in provided. The therapeutic combination includes an immunotherapeutics for treating the cancer, and a peptide having one of SEQ ID NOs. 1-3 and being capable of selectively binding to CXC chemokine receptor 4 (CXCR4). When the peptide of the therapeutic combination binds to CXCR4, an immune microenvironment of the tumor is modulated and/or accessibility of immune cells to the tumor is regulated. A method for treating cancer using the therapeutic combination is also provided.

T-cell lymphomas are a heterogeneous group of malignancies involving T lymphocytes and generally characterized by a poor prognosis. Among them, cutaneous T-cell lymphomas involve primarily the skin. Mycosis fungoides and Sezary syndrome are the most frequent cutaneous T-cell lymphomas. The inventors studied the regulatory T phenotype of Sezary cells and showed the expression of CCR8 (CD198) by Sezary cells and other T-cell lymphoma cell lines. CCR8 therefore appears as a useful diagnostic, prognostic and follow-up marker, and as a potential therapeutic target in T-cell lymphomas. Therapeutic depletion of CCR8-expressing cancer cells would eliminate tumor cells and also activate the anti-tumor immunity in T-cell lymphomas.